Plexin-A3 and plexin-A4 restrict the migration of sympathetic neurons but not their neural crest precursors.
Plexin-A3 and plexin-A4 restrict the migration of sympathetic neurons but not their neural crest precursors.
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Plexin-A3 和 plexin-A4 限制交感神经元的迁移，但不限制其神经嵴前体。
DOI：
10.1016/j.ydbio.2008.01.002
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发表时间：
2008
影响因子：
2.7
通讯作者：
Cheng,Hwai-Jong
中科院分区：
文献类型：
--
作者：
Waimey,KathrynE;Huang,Pei-Hsin;Chen,Maggie;Cheng,Hwai-Jong
在发育过程中，信号素家族的引导分子是交感神经系统正常形成所必需的。丛状蛋白是介导信号素信号的受体，但丛状蛋白在交感神经发育过程中的作用尚不完全清楚。通过对突变小鼠的体内表型分析、表达模式研究和体外分析，我们发现丛状蛋白a3和丛状蛋白a4对正常交感神经发育至关重要。本研究证实了我们之前的体外实验结果，即这两种神经丛对交感神经轴突的引导有不同的调节。此外，我们发现通过丛状蛋白a3和丛状蛋白a4的信号传导限制了交感神经元的迁移，但这两个丛状蛋白的功能是冗余的，因为迁移缺陷仅在丛状蛋白a3 /-A4双突变体中观察到。令人惊讶的是，我们的分析还表明，在到达交感神经原之前，神经丛a3和神经丛a4并不需要引导神经嵴前体。免疫沉淀研究表明，这两个丛蛋白独立介导分泌的信号蛋白信号。因此，丛蛋白a3和丛蛋白a4在新分化的交感神经元中表达，而不是在它们的神经嵴前体中表达。它们共同调节交感神经元的迁移，然后分别引导交感轴突。
During development, the semaphorin family of guidance molecules is required for proper formation of the sympathetic nervous system. Plexins are receptors that mediate semaphorin signaling, but how plexins function during sympathetic development is not fully understood. Using phenotypic analyses of mutant mice in vivo, expression pattern studies, and in vitro assays, we show that plexin-A3 and plexin-A4 are essential for normal sympathetic development. This study confirms our previous in vitro findings that the two plexins differentially regulate the guidance of sympathetic axons. In addition, we find that semaphorin signaling through plexin-A3 and plexin-A4 restricts the migration of sympathetic neurons, but these two plexins function redundantly since migration defects are only observed in plexin-A3/-A4 double mutants. Surprisingly, our analysis also indicates that plexin-A3 and plexin-A4 are not required for guiding neural crest precursors prior to reaching the sympathetic anlagen. Immunoprecipitation studies suggest that these two plexins independently mediate secreted semaphorin signaling. Thus, plexin-A3 and plexin-A4 are expressed in newly-differentiated sympathetic neurons, but not their neural crest precursors. They function cooperatively to regulate the migration of sympathetic neurons and then differentially to guide the sympathetic axons.